R (−)-ketamine shows greater potency and longer lasting antidepressant effects than S (+)-ketamine
This vehicle-controlled mouse study (n=40) compared the antidepressant efficacy between R(-) and S(+) isomer forms of ketamine (10mg/kg) and found that both forms produce rapid antidepressant effects, but only arketamine produces long-lasting antidepressant effects persisting 7 days after a single infusion.
Authors
- Kenji Hashimoto
Published
Abstract
Introduction
The N-methyl-d-aspartate (NMDA) receptor antagonist ketamine is one of the most attractive antidepressants for treatment-resistant major depressive disorder (MDD). Ketamine (or RS (±)-ketamine) is a racemic mixture containing equal parts of R (−)-ketamine and S (+)-ketamine.
Methods
In this study, we examined the effects of R- and S-ketamine on depression-like behavior in juvenile mice after neonatal dexamethasone (DEX) exposure.
Results
In the tail suspension test (TST) and forced swimming test (FST), both isomers of ketamine significantly attenuated the increase in immobility time, seen in DEX-treated juvenile mice at 27 and 29 h respectively, after ketamine injections. In the 1% sucrose preference test (SPT), both isomers significantly attenuated the reduced preference for 1% sucrose consumption in DEX-treated juvenile mice, 48 h after a ketamine injection. Interestingly, when immobility times were tested by the TST and FST at day 7, R-ketamine, but not S-ketamine, significantly lowered the increases in immobility seen in DEX-treated juvenile mice.
Discussion
This study shows that a single dose of R-ketamine produced rapid and long-lasting antidepressant effects in juvenile mice exposed neonatally to DEX. Therefore, R-ketamine appears to be a potent and safe antidepressant relative to S-ketamine, since R-ketamine may be free of psychotomimetic side effects.
Research Summary of 'R (−)-ketamine shows greater potency and longer lasting antidepressant effects than S (+)-ketamine'
Introduction
Growing evidence implicates glutamatergic neurotransmission through the N-methyl-D-aspartate (NMDA) receptor in the neurobiology and treatment of major depressive disorder (MDD). Ketamine, an NMDA receptor antagonist given clinically as the racemic mixture RS (±)-ketamine, produces rapid antidepressant effects in patients with MDD including treatment-resistant cases. The two stereoisomers differ pharmacologically: S (+)-ketamine has about fourfold greater affinity for the NMDA receptor and greater anaesthetic and psychotomimetic potency compared with R (−)-ketamine, but most clinical studies have used the racemate so the relative antidepressant contributions of each isomer remain unclear. Zhang and colleagues set out to compare the antidepressant-like effects of the individual ketamine isomers in an animal model. Using juvenile mice that had been exposed neonatally to dexamethasone (DEX) — a paradigm the investigators previously reported to produce depression-like behaviour — the study examined whether R- and S-ketamine differ in acute and sustained effects on several behavioural assays relevant to depression. The aim was to determine potency and duration of effect for each isomer after a single administration.
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Study Details
- Study Typeindividual
- Journal
- Compounds
- Topics
- Author
- APA Citation
Zhang, J., Li, S., & Hashimoto, K. (2014). R (−)-ketamine shows greater potency and longer lasting antidepressant effects than S (+)-ketamine. Pharmacology Biochemistry and Behavior, 116, 137-141. https://doi.org/10.1016/j.pbb.2013.11.033
References (2)
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